ORCID Profile
0000-0002-0940-3311
Current Organisation
University of Oxford
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: eLife Sciences Publications, Ltd
Date: 17-05-2022
Publisher: eLife Sciences Publications, Ltd
Date: 19-12-2017
DOI: 10.7554/ELIFE.30637
Abstract: Bacteria responsible for the greatest global mortality colonize the human microbiota far more frequently than they cause severe infections. Whether mutation and selection among commensal bacteria are associated with infection is unknown. We investigated de novo mutation in 1163 Staphylococcus aureus genomes from 105 infected patients with nose colonization. We report that 72% of infections emerged from the nose, with infecting and nose-colonizing bacteria showing parallel adaptive differences. We found 2.8-to-3.6-fold adaptive enrichments of protein-altering variants in genes responding to rsp, which regulates surface antigens and toxin production agr, which regulates quorum-sensing, toxin production and abscess formation and host-derived antimicrobial peptides. Adaptive mutations in pathogenesis-associated genes were 3.1-fold enriched in infecting but not nose-colonizing bacteria. None of these signatures were observed in healthy carriers nor at the species-level, suggesting infection-associated, short-term, within-host selection pressures. Our results show that signatures of spontaneous adaptive evolution are specifically associated with infection, raising new possibilities for diagnosis and treatment.
Publisher: eLife Sciences Publications, Ltd
Date: 21-02-2019
Publisher: eLife Sciences Publications, Ltd
Date: 14-06-2022
DOI: 10.7554/ELIFE.77195
Abstract: During severe infections, Staphylococcus aureus moves from its colonising sites to blood and tissues and is exposed to new selective pressures, thus, potentially driving adaptive evolution. Previous studies have shown the key role of the agr locus in S. aureus pathoadaptation however, a more comprehensive characterisation of genetic signatures of bacterial adaptation may enable prediction of clinical outcomes and reveal new targets for treatment and prevention of these infections. Here, we measured adaptation using within-host evolution analysis of 2590 S . aureus genomes from 396 independent episodes of infection. By capturing a comprehensive repertoire of single nucleotide and structural genome variations, we found evidence of a distinctive evolutionary pattern within the infecting populations compared to colonising bacteria. These invasive strains had up to 20-fold enrichments for genome degradation signatures and displayed significantly convergent mutations in a distinctive set of genes, linked to antibiotic response and pathogenesis. In addition to agr -mediated adaptation, we identified non-canonical, genome-wide significant loci including sucA-sucB and stp1 . The prevalence of adaptive changes increased with infection extent, emphasising the clinical significance of these signatures. These findings provide a high-resolution picture of the molecular changes when S. aureus transitions from colonisation to severe infection and may inform correlation of infection outcomes with adaptation signatures.
Publisher: eLife Sciences Publications, Ltd
Date: 17-12-2019
DOI: 10.7554/ELIFE.45833
Abstract: Quantifying pathogen transmission in multi-host systems is difficult, as exemplified in bovine tuberculosis (bTB) systems, but is crucial for control. The agent of bTB, Mycobacterium bovis, persists in cattle populations worldwide, often where potential wildlife reservoirs exist. However, the relative contribution of different host species to bTB persistence is generally unknown. In Britain, the role of badgers in infection persistence in cattle is highly contentious, despite decades of research and control efforts. We applied Bayesian phylogenetic and machine-learning approaches to bacterial genome data to quantify the roles of badgers and cattle in M. bovis infection dynamics in the presence of data biases. Our results suggest that transmission occurs more frequently from badgers to cattle than vice versa (10.4x in the most likely model) and that within-species transmission occurs at higher rates than between-species transmission for both. If representative, our results suggest that control operations should target both cattle and badgers.
Publisher: eLife Sciences Publications, Ltd
Date: 25-07-2019
Publisher: Cold Spring Harbor Laboratory
Date: 14-03-2017
DOI: 10.1101/116681
Abstract: Bacteria responsible for the greatest global mortality colonize the human microbiome far more frequently than they cause severe infections. Whether mutation and selection within the microbiome accompany infection is unknown. We investigated de novo mutation in 1163 Staphylococcus aureus genomes from 105 infected patients with nose-colonization. We report that 72% of infections emerged from the microbiome, with infecting and nose-colonizing bacteria showing parallel adaptive differences. We found 2.8-to-3.6-fold enrichments of protein-altering variants in genes responding to rsp , which regulates surface antigens and toxicity agr , which regulates quorum-sensing, toxicity and abscess formation and host-derived antimicrobial peptides. Adaptive mutations in pathogenesis-associated genes were 3.1-fold enriched in infecting but not nose-colonizing bacteria. None of these signatures were observed in healthy carriers nor at the species-level, suggesting disease-associated, short-term, within-host selection pressures. Our results show that infection, like a cancer of the microbiome, emerges through spontaneous adaptive evolution, raising new possibilities for diagnosis and treatment. Life-threatening S. aureus infections emerge from nose microbiome bacteria in association with repeatable adaptive evolution.
Publisher: eLife Sciences Publications, Ltd
Date: 22-02-2019
DOI: 10.7554/ELIFE.42486
Abstract: Pyomyositis is a severe bacterial infection of skeletal muscle, commonly affecting children in tropical regions, predominantly caused by Staphylococcus aureus. To understand the contribution of bacterial genomic factors to pyomyositis, we conducted a genome-wide association study of S. aureus cultured from 101 children with pyomyositis and 417 children with asymptomatic nasal carriage attending the Angkor Hospital for Children, Cambodia. We found a strong relationship between bacterial genetic variation and pyomyositis, with estimated heritability 63.8% (95% CI 49.2–78.4%). The presence of the Panton–Valentine leucocidin (PVL) locus increased the odds of pyomyositis 130-fold (p=10-17.9). The signal of association mapped both to the PVL-coding sequence and to the sequence immediately upstream. Together these regions explained over 99.9% of heritability (95% CI 93.5–100%). Our results establish staphylococcal pyomyositis, like tetanus and diphtheria, as critically dependent on a single toxin and demonstrate the potential for association studies to identify specific bacterial genes promoting severe human disease.
Publisher: Cold Spring Harbor Laboratory
Date: 12-02-2022
DOI: 10.1101/2022.02.11.480068
Abstract: During severe infections, Staphylococcus aureus moves from its colonising sites to blood and tissues, and is exposed to new selective pressures, thus potentially driving adaptive evolution. Previous studies have shown the key role of the agr locus in S. aureus pathoadaptation, however a more comprehensive characterisation of genetic signatures of bacterial adaptation may enable prediction of clinical outcomes and reveal new targets for treatment and prevention of these infections. Here, we measured adaptation using within-host evolution analysis of 2,590 S. aureus genomes from 396 independent episodes of infection. By capturing a comprehensive repertoire of single-nucleotide and structural genome variations, we found evidence of a distinctive evolutionary pattern within the infecting populations compared to colonising bacteria. These invasive strains had up to 20-fold enrichments for genome degradation signatures and displayed significantly convergent mutations in a distinctive set of genes, linked to antibiotic response and pathogenesis. In addition to agr -mediated adaptation we identified non-canonical, genome-wide significant loci including sucA - sucB and stp1 . The prevalence of adaptive changes increased with infection extent, emphasising the clinical significance of these signatures. These findings provide a high-resolution picture of the molecular changes when S. aureus transitions from colonisation to severe infection and may inform correlation of infection outcomes with adaptation signatures.
Publisher: Springer Science and Business Media LLC
Date: 19-10-2023
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Daniel Wilson.